Background:
Each year, more than 32,000 people in the United States are diagnosed with colorectal cancer that has returned or progressed after treatment and spread to other organs. This is called metastatic colorectal cancer (mCRC). Most people with mCRC survive only about 2 years.
Objective:
To test the ability of a combination of up to 4 experimental anti-cancer drugs treat mCRC. The names of these drugs are retifanlimab, TriAdeno vaccine, N-803, and SX-682. They are described below.
Eligibility:
Adults aged 18 years or older with mCRC. Participants must have
Design:
Participants will be screened. This includes having a physical exam, blood tests, urine tests, and imaging tests. If signed on to the study, participants will have 2 tumor biopsies. One when starting the study and once about 8 weeks after bring on the study. Participants will receive $500 for each biopsy.
Participants will be treated with either 3 or 4 drugs and will receive a detailed calendar explaining when each drug is given.
Retifanlimab is given every 4 weeks through an IV (an IV is tube attached to a needle inserted into a vein in the arm). N-803 is injected under the skin on the abdomen every 4 weeks.
TriAdeno vaccine is injected under the skin of the upper arm or thigh once a month for 3 doses and then once every 3 months.
Some participants will also receive a 4th drug. SX-682 is a pill taken by mouth. Participants will take this drug 2 times a day at home for about 3 weeks of each month.
Study treatment will continue up to 2 years. Follow-up phone calls/emails may continue for 3 more years.
Participants with histologically confirmed colorectal cancer and evidence of metastatic disease.
Participants must have received, been ineligible to receive, or refused to receive two lines of standard systemic therapy i.e., a fluoropyrimidine with oxaliplatin or irinotecan with bevacizumab, regorafenib, trifluridine, and (if history of RAS wild-type) EGFR-targeted therapy. Participants must have received one line of systemic checkpoint inhibitor if history of advanced microsatellite instability-high [MSI-H/dMMR]) metastatic colon cancer.
Participants who had progressive disease within 6 months before study treatment following standard adjuvant therapy are eligible if they have not received systemic therapy for metastatic disease. Participants with a history of MSI-H/dMMR must have also received one line of checkpoint inhibitor therapy.
Age >= 18 years.
Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior therapeutic radiotherapy within 14 days prior to study treatment initiation.
Participants with palliative radiotherapy performed within 7 days prior to study treatment initiation.
intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections in participants with asthma
using topical, ocular, intra-articular, or intranasal corticosteroids (with minimal systemic absorption
Sequential
Retifanlimab
Drug500 mg infused via IV over 30 minutes every 28 days
Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform
Biological/Vaccine5x10\^11 virus particles per 1 mL administered via subcutaneous injection in the upper arm and anterolateral upper thigh on Day 1 of Cycles 1, 2, 3 and every 3 cycles after that
N-803
Drug15 ug/kg administered via subcutaneous injection to the abdomen every 28 days
SX-682
Drug200 mg administered orally twice per day on days 6-26 of every cycle
Phase I: Safety profiles of the IO regimens consisting of retifanlimab, TriAdeno vaccine, N-803 (A1), and retifanlimab, TriAdeno vaccine, N-803, SX-682 (A2) in participants with metastatic colorectal cancer
Number of DLTs within DLT period (C1 days 1-28). Any toxicities identified.
Phase II: Overall response rate (ORR) defined as the CR+PR of the IO regimen in mCRC
The fraction of participants with a CR or PR (per RECIST v1.1) in Phase II will be reported along with a 95% confidence interval.
Progression Free Survival (PFS) at 6, 12, and 24 months
PFS will be determined by the Kaplan-Meier method and reported at 6, 12, and 24 months from the date the participant was enrolled in the trial, along with 95 percent confidence intervals at these times.
Disease control rate (DCR) at 6 and 12 months
DCR at 6 and 12 months will be reported as a fraction along with a 95 percent confidence interval for each.
Safety during Phase II
AEs will be reported by type and grade within Phase II.
Overall survival
Monitoring of participants from Day 1 of each cycle, at follow up visits and until date of death/closure of the study.
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